Apparatus and method for diagnosis of optically identifiable ophthalmic conditions

ABSTRACT

An apparatus that measures images of at least a portion of an eye and records data sets indicative of a neurological condition. A method of the invention employs a plurality of images, or a plurality of data sets, or at least one image and at least one data set to provide an interpretive result based on the interrelation of the images and data sets, such as by superposition. The apparatus and method thereby provide guidance as to the presence of a medical condition in a patient. The apparatus includes modules that observe images and/or data sets, that analyze the information, and that superpose the information. Modules are provided to store information, to provide data output, to provide reports, and to display information, including superposed images and data. Modules can be provided in hardware, in software, in firmware, or in combinations thereof.

FIELD OF THE INVENTION

The invention relates to testing for physiological and neurologicalconditions in general and particularly to systems and methods thatemploy optical imaging of an eye and the responses of individuals tovisual stimuli.

BACKGROUND OF THE INVENTION

Numerous systems and methods are known for examining states of health ofeyes. For example, U.S. Pat. No. 5,065,767, issued Nov. 19, 1991 toMaddess, discloses a psychophysical method for diagnosing glaucoma thatemploys a time varying contrast pattern. Glaucoma may be indicated foran individual who displays a higher than normal contrast threshold forobserving the pattern. Maddess also discloses other tests for glaucomasuch as the well-known observation of a scotoma, measurement ofintraocular pressure, and assessment of color vision defects. U.S. Pat.No. 5,295,495, issued Mar. 24, 1994 to Maddess, discloses systems andmethods for diagnosing glaucoma using an individual's response tohorizontally moving stripe patterns, which is known as optokineticnystagmus (OKN). The spatially varying patterns may also varytemporally. In U.S. Pat. No. 5,539,482, issued Jul. 23, 1996 to James etal., additional systems and methods for diagnosing glaucoma usingspatial as well as temporal variations in contrast patterns aredisclosed. U.S. Pat. No. 5,912,723, issued Jun. 15, 1999 to Maddess,discloses systems and methods that use a plurality of spatially andtemporally varying contrast patterns to improve the methods disclosed inthe earlier patents. U.S. Pat. No. 6,315,414, issued Nov. 13, 2001 toMaddess et al., describes systems and methods for making a binocularassessment of possible damage to the optical nerve, optical radiationsand white matter of the visual brain indicative of various neurologicaldisorders by measuring responses to visual stimuli.

U.S. Pat. No. 6,068,377, issued May 30, 2000 to McKinnon et al.,describes systems and methods for testing for glaucoma using a frequencydoubling phenomenon produced by isoluminent color visual stimuli. Thedisclosure is similar to that of Maddess and co-workers, but usesdifferent, preferably complementary, frequencies of light having thesame luminosity as the visual probe signal.

U.S. Pat. Nos. 5,713,353 and 6,113,537 describe systems and methods fortesting for blood glucose level using light patterns that vary inintensity, color, rate of flicker, spatial contrast, detail content andor speed. The approach described involves measuring the response of aperson to one or more light pattern variations and deducing a bloodglucose level by comparing the data to calibration data.

Other disease conditions and their identification are described in apaper by S. Sokol, entitled “The visually evoked cortical potential inthe optic nerve and visual pathway disorders,” which was published inElectrophysiological testing in diseases of the retina, optic nerve, andvisual pathway, edited by G. A. Fishman, published by the AmericanAcademy of Ophthalmology, of San Francisco, in 1990, Volume 2, Pages105-141. An article by Clark Tsai, entitled “Optic Nerve Head and NerveFiber Layer in Alzheimer's Disease,” which was published in Arch. ofOphthalmology, Vol. 107, February, 1991, states that large diameterneurons are damaged in Alzheimer's disease.

U.S. Pat. No. 5,474,081, issued Dec. 12, 1995 to Livingstone et al.,describes systems and methods for determining magnocellular defect anddyslexia by presenting temporally and spatially varying patterns, anddetecting visually evoked potentials (VEP) using an electrode assemblyin contact with the subject being tested.

U.S. Pat. No. 6,129,682, issued Oct. 10, 2000 to Borchert et al.,discloses systems and methods for non-invasively measuring intracranialpressure from measurements of an eye, using an imaging scan of theretina of an eye and a measurement of intraocular pressure. Theintraocular pressure is measured by standard ocular tonometry, which isa procedure that generally involves contact with the eye. U.S. Pat. Nos.5,830,139, 6,120,460, 6,123,668, 6,123,943, 6,312,393 and 6,423,001describe various systems and methods that involve mechanical contactwith an eye in order to perform various tests. Direct physical contactwith an eye involves potential discomfort and risk of injury throughinadvertent application of force or transfer of harmful chemical orbiological material to the eye. Direct physical contact with an eye isalso potentially threatening to some patients, especially those who areyoung or who may not fully understand the test that is being performed.

First Generation FDT Instrument

The Frequency Doubling Technique (hereinafter “FDT”) presents back-litflashed images viewed on a fixed, flat shielded screen in front of astationary subject. The FDT instrument is similar, but smaller, and theFDT test is substantially shorter in testing duration, as compared to avisual field instrument that tests peripheral and central vision. Visualfield testing is standard in all offices providing comprehensive eyeexams and treatment of eye disease. The FDT instrument uses sinusoidalgrating targets of low spatial frequency (as opposed to simple dots oflight in a traditional visual field test). The sinusoidal gratings arereversed (black to white, and white to black) at 25 Hz. The subjectperceives the targets as small striped areas in either central orperipheral vision. As with traditional visual field testing, subjectsare seated and have the chin and forehead positioned in a stabilizingrest support. Generally, subjects are tested monocularly. They fixate atarget directly in front of them and respond by pushing a button eachtime they see an image flashed anywhere in their visual field. Theinstrument records and retests areas based on the subject's responses. Acomputer program operating on a processor calculates reliability basedon fixation losses. The entire test takes less than two minutes per eye.The FDT does not require dilation of the subject's eyes. Therefore, itdoes not impair vision or the ability to function after the test isperformed. The test causes no discomfort. The FDT has received approvalfrom the Federal Drug Administration and has been in clinical use forover four years.

There is a need for systems and methods that will provide betterinformation about a larger number of possible conditions using a singletesting period, and that will disclose the initial levels of impairmentat accuracies that are not presently attainable, while avoiding to theextent possible mechanical contact with the test subject, especiallycontact with the eye. There is also a need for systems and methods thatcan be used by non-specialist medical practitioners to screen andevaluate patients without the necessity to first involve a specialistpractitioner.

SUMMARY OF THE INVENTION

The invention uses more than one observation selected from imagingmethods and responses (e.g., a “data set”) of a person to provide anassessment of a state of health or medical condition of the person. Theimages are obtained from any imaging method that provides imageinformation about a portion of an eye. The responses or data sets areobtained as the response of a person to a test that elicits voluntary orinvoluntary responses that provide information about a neurologicalstate or condition of the person. The invention combines or correlatesinformation from the more than one observation to provide theassessment.

In one aspect, the invention relates to an apparatus for performingmultiple procedures involving the eye. The apparatus comprises at leastone imager for imaging at least a portion of an eye of a patient, the atleast one imager configured to provide image data comprises at least twodata types selected from the group consisting of data from ophthalmicimages using confocal microscopy data, retinal polarimetry data, opticalcoherence tomography data, thermal image data, spectroscopic image data,refractometry data, and visible image data and a data analysis modulethat interrelates data from the at least two data types to provide ainterpretive result.

In one embodiment, the apparatus further comprises a display module thatprovides a display of analyzed data to a user. In one embodiment, theapparatus further comprises a display module that provides a display ofanalyzed data to a user using a false color representation for thedisplayed data.

In some embodiments, the apparatus further comprises a data outputmodule that reports the interrelated data from the at least two datatypes. In some embodiments, the apparatus further comprises a reportmodule that reports the interpretive result. In some embodiments, theapparatus further comprises a single output module that reports theinterrelated data from the at least two data types and the interpretiveresult. In some embodiments, the apparatus further comprises asuperposition module for superimposing data obtained from at least twoimages.

In some embodiments, the superposition module comprises a module thatidentifies a fiduciary point in each image to be superimposed, each thefiduciary point representing substantially the same point in the eye; amodule that, as necessary, orients an image to be superimposed about thefiduciary point so that a first metric and a second metric are orientedin selected orientations; a module that, as necessary, scales an imageso that a first unit of measure associated with the first metric and asecond unit of measure associated with the second metric aresubstantially equal to selected first and second values in each image tobe superimposed; and a module that creates a one-to-one correspondencebetween the fiduciary point, the first metric and the second metric in afirst image to be superimposed with the fiduciary point, the firstmetric and the second metric in a second image to be superimposed.

In some embodiments, the first metric is a first axial direction, thesecond metric is a second axial direction that is coplanar with but notparallel to the first axial direction, the first unit of measureassociated with the first metric is a length along the first axialdirection, and the second unit of measure associated with the secondmetric is a length along the second axial direction. In someembodiments, the first metric is a first axial direction, the secondmetric is an angular displacement from the first axial direction, thefirst unit of measure associated with the first metric is a length alongthe first axial direction, and the second unit of measure associatedwith the second metric is a unit of angular measure. In someembodiments, the superposition module comprises a module that identifiesa first fiduciary point in each image to be superimposed, each of thefirst fiduciary points representing substantially the same point in theeye; a module that identifies a second fiduciary point in each image tobe superimposed, each of the second fiduciary points representingsubstantially the same point in the eye; a module that, as necessary,scales an image so that a distance between the first fiduciary point andthe second fiduciary point in the image is substantially equal to adistance between the first fiduciary point and the second fiduciarypoint in another of the at least two images to be superimposed; and amodule that creates a one-to-one correspondence between the first andsecond fiduciary points of the first image and the second image of theat least two images to be superimposed.

In some embodiments, the apparatus further comprises a display fordisplaying the superimposed data obtained from at least two images. Insome embodiments, the superimposed data obtained from at least twoimages comprises data obtained from at least two different data typesselected from the group consisting of data from ophthalmic images usingconfocal microscopy data, retinal polarimetry data, optical coherencetomography data, thermal image data, spectroscopic image data, andvisible image data. In some embodiments, the apparatus further comprisesa memory for storing image data. In some embodiments, the memory forstoring image data is configured to store and to selectively retrievedata from at least one image for determining changes induced in responseto an applied stress. In some embodiments, the applied stress isselected from the group consisting of intra ocular pressure variation,blood pressure variation, oxygen concentration variation, exercise,flashing light, drug administration, administration of insulin, andadministration of glucose. In some embodiments, the memory is configuredto store and to selectively retrieve data from at least one image fordetermining a time evolution of changes induced in response to anapplied stress. In some embodiments, the memory for storing image datais configured to selectively retrieve data from at least one image fortrending analysis purposes. In some embodiments, the memory for storingimage data is configured to archivally store image data.

In some embodiments, the apparatus further comprises means for aligningthe image of the eye of a patient. In some embodiments, the alignmentmeans operates automatically based on the movement of the eye of apatient relative to the imaging means. In some embodiments, thealignment means includes a fixation pattern for focusing a macula of theeye thereon.

In some embodiments, the data analysis module is configured toautomatically determine a presence of an abnormality. In someembodiments, the data analysis module is configured to automaticallydetermine an extent of the abnormality. In some embodiments, the dataanalysis module comprises a scaling module for providing a scaledestimation of the extent of the abnormality. In some embodiments, thedata analysis module is configured to automatically determine a changein the extent of the abnormality over time.

In some embodiments, the apparatus further comprises an informationinput module for inputting other patent-related information including atleast one from the group of tonometer intraocular pressure,patient-history, family history, blood pressure, vital signs, medicationand pupillometry.

In another aspect the invention feature an apparatus for performingmultiple procedures involving the eye. The apparatus comprises a datacollection apparatus for collecting a data set corresponding to at leasta portion of an eye of a patient, the data collection apparatusconfigured to provide data indicative of at least two neurologicaldisorders selected from the group consisting of glaucoma, maculardegeneration, diabetic retinopathy, Parkinson's disease, Alzheimer'sdisease, dyslexia, multiple sclerosis, optic neuritis, LDS, head trauma,diabetes, and inappropriate responses to contrast sensitivity patterns;and a data analysis module that interrelates the data indicative of atleast two neurological disorders to provide a interpretive result.

In some embodiments, the apparatus further comprises a map generationmodule for generating a map indicative of the presence of a selected oneof glaucoma, macular degeneration, and inappropriate responses tocontrast sensitivity patterns. In some embodiments, the apparatusfurther comprises a measurement module for measuring a loss or anapparent loss of ganglion cells associated with a selected one ofdiabetic retinopathy, Parkinson's disease, and Alzheimer's disease. Insome embodiments, the apparatus further comprises a data generatingmodule for generating data indicative of the presence of a selected onof dyslexia, multiple sclerosis, and optic neuritis. In someembodiments, the apparatus further comprises a data output module thatreports the interrelated data from the data set. In some embodiments,the apparatus further comprises a report module that reports theinterpretive result. In some embodiments, the apparatus furthercomprises a single output module that reports the interrelated data fromthe data set and the interpretive result.

In some embodiments, the apparatus further comprises a superpositionmodule for superimposing data obtained from at least two data sets. Insome embodiments, the superposition module comprises a module thatidentifies a fiduciary point in each data set to be superimposed, eachthe fiduciary point representing substantially the same point in theeye; a module that, as necessary, orients data to be superimposed aboutthe fiduciary point so that a first metric and a second metric areoriented in selected orientations; a module that, as necessary, scales adata set so that a first unit of measure associated with the firstmetric and a second unit of measure associated with the second metricare substantially equal to selected first and second values in each dataset to be superimposed; and a module that creates a one-to-onecorrespondence between the fiduciary point, the first metric and thesecond metric in a first data set to be superimposed with the fiduciarypoint, the first metric and the second metric in a second data set to besuperimposed. In some embodiments, the first metric is a first axialdirection, the second metric is a second axial direction that iscoplanar with but not parallel to the first axial direction, the firstunit of measure associated with the first metric is a length along thefirst axial direction, and the second unit of measure associated withthe second metric is a length along the second axial direction. In someembodiments, the first metric is a first axial direction, the secondmetric is an angular displacement from the first axial direction, thefirst unit of measure associated with the first metric is a length alongthe first axial direction, and the second unit of measure associatedwith the second metric is a unit of angular measure.

In some embodiments, the superposition module comprises a module thatidentifies a first fiduciary point in each data set to be superimposed,each the first fiduciary point representing substantially the same pointin the eye; a module that identifies a second fiduciary point in eachdata set to be superimposed, each the second fiduciary pointrepresenting substantially the same point in the eye; a module that, asnecessary, scales a data set so that a distance between the firstfiduciary point and the second fiduciary point in the data set issubstantially equal to a distance between the first fiduciary point andthe second fiduciary point in another of the at least two data sets tobe superimposed; and a module that creates a one-to-one correspondencebetween the first and second fiduciary points of the first data set andthe second data set of the at least two data sets to be superimposed. Insome embodiments, the apparatus further comprises a display fordisplaying the superimposed data obtained from at least two data sets.

In some embodiments, the superimposed data obtained from at least twodata sets comprises image data indicative of at least one neurologicaldisorder selected from the group consisting of glaucoma, maculardegeneration, diabetic retinopathy, Parkinson's disease, Alzheimer'sdisease, dyslexia, multiple sclerosis, optic neuritis, LDS, head trauma,diabetes, and inappropriate responses to contrast sensitivity patterns.

In some embodiments, the apparatus further comprises a memory forstoring data. In some embodiments, the memory for storing data isconfigured to store and to selectively retrieve data from at least onedata set for determining changes induced in response to an appliedstress. In some embodiments, the applied stress is selected from thegroup consisting of intra ocular pressure variation, blood pressurevariation, oxygen concentration variation, exercise, flashing light,drug administration, administration of insulin, and administration ofglucose. In some embodiments, the memory is configured to store and toselectively retrieve data from at least one data set for determining atime evolution of changes induced in response to an applied stress. Insome embodiments, the memory for storing data is configured toselectively retrieve data from at least one data set for trendinganalysis purposes. In some embodiments, the memory for storing data isconfigured to archivally store data.

In some embodiments, the apparatus further comprises means for aligningan eye of a patient. In some embodiments, the alignment means operatesautomatically based on the movement of the eye of a patient relative tothe data collection means. In some embodiments, the alignment meansincludes a fixation pattern for focusing a macula of the eye thereon.

In some embodiments, the apparatus further comprises means forperforming at least one objective eye-related interpretive procedurerelating to a neurological disorder. In some embodiments, the at leastone objective eye-related interpretive procedure includes at least oneof PERG, OKN and VEP. In one embodiment, the apparatus further comprisesa display module that provides a display of analyzed data to a user. Inone embodiment, the apparatus further comprises a display module thatprovides a display of analyzed data to a user using a false colorrepresentation for the displayed data.

In some embodiments, the data analysis module is configured toautomatically determine a presence of an abnormality. In someembodiments, the data analysis module is configured to automaticallydetermine an extent of the abnormality. In some embodiments, the dataanalysis module comprises a scaling module for providing a scaledestimation of the extent of the abnormality. In some embodiments, thedata analysis module is configured to automatically determine a changein the extent of the abnormality over time.

In some embodiments, the apparatus further comprises an informationinput module for inputting other patent-related information including atleast one from the group of tonometer intraocular pressure,patient-history, family history, blood pressure, vital signs, medicationand pupillometry.

In a further aspect the invention features an apparatus for performingmultiple procedures involving the eye. The apparatus comprises an imagerfor imaging at least a portion of an eye of a patient, the imagerconfigured to provide image data; a data collection apparatus forcollecting a data set corresponding to at least a portion of an eye of apatient, the data collection apparatus configured to provide dataindicative of a neurological disorders; and a data analysis module thatinterrelates the image data and the data indicative of a neurologicaldisorder to provide a interpretive result.

In one embodiment, the image data comprises a data type selected fromthe group consisting of data from ophthalmic images using confocalmicroscopy data, retinal polarimetry data, optical coherence tomographydata, thermal image data, spectroscopic image data, refractometry data,and visible image data. In one embodiment, the neurological disorder isselected from the group consisting of glaucoma, macular degeneration,diabetic retinopathy, Parkinson's disease, Alzheimer's disease,dyslexia, multiple sclerosis, optic neuritis, LDS, head trauma,diabetes, and inappropriate responses to contrast sensitivity patterns.

In some embodiments, the apparatus further comprises a data outputmodule that reports the interrelated data from the image data and thedata indicative of a neurological disorder.

In some embodiments, the apparatus further comprises a report modulethat reports the interpretive result. In some embodiments, the apparatusfurther comprises a single output module that reports the interrelateddata from the image data and the data indicative of a neurologicaldisorder and the interpretive result. In one embodiment, the apparatusfurther comprises a display module that provides a display of analyzeddata to a user. In one embodiment, the apparatus further comprises adisplay module that provides a display of analyzed data to a user usinga false color representation for the displayed data.

In some embodiments, the apparatus further comprises a superpositionmodule for superimposing data obtained from an image and data indicativeof a neurological disorder. In some embodiments, the superpositionmodule comprises a module that identifies a fiduciary point in the imageto be superimposed, and a fiduciary point in the data indicative of aneurological disorder, each the fiduciary point representingsubstantially the same point in the eye; a module that, as necessary,orients at least one of the image and the data indicative of aneurological disorder to be superimposed about the fiduciary point sothat a first metric and a second metric are oriented in selectedorientations; a module that, as necessary, scales at least one of theimage and the data indicative of a neurological disorder so that a firstunit of measure associated with the first metric and a second unit ofmeasure associated with the second metric are substantially equal toselected first and second values in each of the image and the dataindicative of a neurological disorder to be superimposed; and a modulethat creates a one-to-one correspondence between the fiduciary point,the first metric and the second metric in the image to be superimposedwith the fiduciary point, the first metric and the second metric in thedata indicative of a neurological disorder to be superimposed. In someembodiments, the first metric is a first axial direction, the secondmetric is a second axial direction that is coplanar with but notparallel to the first axial direction, the first unit of measureassociated with the first metric is a length along the first axialdirection, and the second unit of measure associated with the secondmetric is a length along the second axial direction. In someembodiments, the first metric is a first axial direction, the secondmetric is an angular displacement from the first axial direction, thefirst unit of measure associated with the first metric is a length alongthe first axial direction, and the second unit of measure associatedwith the second metric is a unit of angular measure. In someembodiments, the superposition module comprises a module that identifiesa first fiduciary point in each of the image and the data indicative ofa neurological disorder to be superimposed, each the first fiduciarypoint representing substantially the same point in the eye; a modulethat identifies a second fiduciary point in each of the image and thedata indicative of a neurological disorder to be superimposed, each thesecond fiduciary point representing substantially the same point in theeye; a module that, as necessary, scales an image so that a distancebetween the first fiduciary point and the second fiduciary point in theimage is substantially equal to a distance between the first fiduciarypoint and the second fiduciary point in the data indicative of aneurological disorder to be superimposed; and a module that creates aone-to-one correspondence between the first and second fiduciary pointsof the image and the data indicative of a neurological disorder to besuperimposed.

In some embodiments, the apparatus further comprises a display fordisplaying the superimposed data obtained from the image and the dataindicative of a neurological disorder. In some embodiments, theapparatus further comprises a memory for storing data, the datacomprises at least one of image data and data indicative of aneurological disorder. In some embodiments, the memory for storing datais configured to store and to selectively retrieve data for determiningchanges induced in response to an applied stress. In some embodiments,the applied stress is selected from the group consisting of intra ocularpressure variation, blood pressure variation, oxygen concentrationvariation, exercise, flashing light, drug administration, administrationof insulin, and administration of glucose. In some embodiments, thememory is configured to store and to selectively retrieve data fordetermining a time evolution of changes induced in response to anapplied stress. In some embodiments, the memory for storing data isconfigured to selectively retrieve data for trending analysis purposes.In some embodiments, the memory for storing data is configured toarchivally store data.

In some embodiments, the apparatus further comprises means for aligningthe image of the eye of a patient. In some embodiments, the alignmentmeans operates automatically based on the movement of the eye of apatient relative to the imaging means. In some embodiments, thealignment means includes a fixation pattern for focusing a macula of theeye thereon.

In some embodiments, the apparatus further comprises means forperforming at least one objective eye-related interpretive procedure. Insome embodiments, the at least one objective eye-related interpretiveprocedure includes at least one of PERG, OKN and VEP. In one embodiment,the apparatus further comprises a display module that provides a displayof analyzed data to a user. In one embodiment, the apparatus furthercomprises a display module that provides a display of analyzed data to auser using a false color representation for the displayed data.

In some embodiments, the data analysis module is configured toautomatically determine a presence of an abnormality. In someembodiments, the data analysis module is configured to automaticallydetermine an extent of the abnormality. In some embodiments, the dataanalysis module comprises a scaling module for providing a scaledestimation of the extent of the abnormality. In some embodiments, thedata analysis module is configured to automatically determine a changein the extent of the abnormality over time.

In some embodiments, the apparatus further comprises an informationinput module for inputting other patent-related information including atleast one from the group of tonometer intraocular pressure,patient-history, family history, blood pressure, vital signs, medicationand pupillometry.

In yet a further aspect, the invention relates to a method of treating apatient. The method comprises the steps of performing an examination ofa patient using the apparatus described in any of the first threeaspects of the invention and treating the patient based at least in parton a result obtained from the examination. In some embodiments, themethod of treatment further comprises the step of providing thetreatment based at least in part on information stored in a memory.

In a further aspect, the invention features a computer program recordedon a machine-readable medium. The computer program comprises a dataanalysis module that interrelates at least two data types, the at leasttwo data types selected from the group consisting of data fromophthalmic images using confocal microscopy data, retinal polarimetrydata, optical coherence tomography data, thermal image data,spectroscopic image data, refractometry data, and visible image data.

In a still further aspect the invention relates to a computer programrecorded on a machine-readable medium. The computer program comprises adata analysis module that interrelates at least two types of dataindicative of a neurological disorder selected from the group consistingof inappropriate responses to contrast sensitivity patterns, glaucoma,macular degeneration, diabetic retinopathy, Parkinson's disease,Alzheimer's disease, dyslexia, multiple sclerosis, and optic neuritis.

In yet a further aspect the invention features a computer programrecorded on a machine-readable medium. The computer program comprises adata analysis module that interrelates image data and data indicative ofa neurological disorder, the image data comprises a data type selectedfrom the group consisting of data from ophthalmic images using confocalmicroscopy data, retinal polarimetry data, optical coherence tomographydata, thermal image data, spectroscopic image data, refractometry data,and visible image data, and the data indicative of a neurologicaldisorder selected from the group consisting of glaucoma, maculardegeneration, diabetic retinopathy, Parkinson's disease, Alzheimer'sdisease, dyslexia, multiple sclerosis, optic neuritis, LDS, head trauma,diabetes, and inappropriate responses to contrast sensitivity patterns.

In a further aspect, the invention relates to a method of diagnosis of astate of health of a patient. The method comprises the steps of imagingat least a portion of an eye of a patient to obtain image data comprisesat least two data types selected from the group consisting of data fromophthalmic images using confocal microscopy data, retinal polarimetrydata, optical coherence tomography data, thermal image data,spectroscopic image data, refractometry data, and visible image data;and interrelating the data from the at least two data types to provide ainterpretive result.

In another aspect, the invention features a method of diagnosis of astate of health of a patient. The method comprises the steps of imagingat least a portion of an eye of a patient to obtain image dataindicative of at least two neurological disorders selected from thegroup consisting of glaucoma, macular degeneration, diabeticretinopathy, Parkinson's disease, Alzheimer's disease, dyslexia,multiple sclerosis, optic neuritis, LDS, head trauma, diabetes, andinappropriate responses to contrast sensitivity patterns; andinterrelating the image data indicative of the at least two neurologicaldisorders to provide a interpretive result.

In still another aspect, the invention relates to a method of diagnosisof a state of health of a patient. The method comprises the steps ofimaging at least a portion of an eye of a patient to obtain image datacomprises a data type selected from the group consisting of data fromophthalmic images using confocal microscopy data, retinal polarimetrydata, optical coherence tomography data, thermal image data,spectroscopic image data, refractometry data, and visible image data,and data indicative of a neurological disorder selected from the groupconsisting of glaucoma, macular degeneration, diabetic retinopathy,Parkinson's disease, Alzheimer's disease, dyslexia, multiple sclerosis,optic neuritis, LDS, head trauma, diabetes, and inappropriate responsesto contrast sensitivity patterns; and interrelating the image data andthe data indicative of a neurological disorder to provide a interpretiveresult.

The foregoing and other objects, aspects, features, and advantages ofthe invention will become more apparent from the following descriptionand from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The objects and features of the invention can be better understood withreference to the drawings described below, and the claims. The drawingsare not necessarily to scale, emphasis instead generally being placedupon illustrating the principles of the invention. In the drawings, likenumerals are used to indicate like parts throughout the various views.

FIG. 1A is a prior art diagram showing some of the physiology of the eyeand the brain in humans;

FIG. 1B depicts a prior art cross sectional diagram showing a feedbackloop from the visual cortex to the LGN;

FIG. 2 is a schematic representation of an exemplary apparatus suitablefor use according to the invention;

FIG. 3A shows a schematic diagram of the disposition of an eyemonitoring device relative to an eye of a person being tested accordingto the invention;

FIG. 3B shows a diagram that depicts the interrelationship among thefeatures of an eye of a person being tested, and the areas of the eyesensed by two sensors, according to the invention;

FIG. 3C shows a diagram that depicts the interrelationship between thefeatures of an eye of a person being tested, and the areas of the eyesensed by one sensor, according to the invention;

FIG. 3D shows a diagram that depicts a test pattern and a fixationsignal that is useful for fixating an eye of a person being tested whenone sensor is employed in the eye monitoring device, according to theinvention;

FIG. 4 is a flow chart showing the steps in the operation of theinstrument of the invention, or alternatively, showing theinterrelationships among the modules comprising apparatus according tothe invention;

FIG. 5 is a diagram that shows components of a superposition moduleaccording to the invention;

FIG. 6 is a diagram showing a region of frequency space having bothtemporal and spatial frequency variations, and indicating a typicalperson's reaction thereto, as is known in the prior art;

FIGS. 7A and 7B are drawings that depict a display space that issegmented and includes an illustrative contrast pattern, as is known inthe prior art;

FIGS. 8A, 8B and 8C are diagrams that show the relationship between animage and a data set, two images taken at different times, and a seriesof images, false color data representations, and data sets,respectively, according to principles of the invention;

FIG. 9 is a schematic showing the relationship among superimposed imagesand/or data sets, according to principles of the invention; and

FIG. 10 shows a hand-held apparatus that measures a person's visualcontrast sensitivity according to principles of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides systems and methods for determining a wide rangeof possible medical conditions, including normal health, the early (oronset) stage of a disease condition, and the development of the diseasecondition up to a fully presented disease conditions (e.g., diagnosis,staging, and monitoring). The invention provides the ability to diagnosethe severity of various disease conditions. By application of themethods of the invention over time, one can monitor the rate and extentof evolution of various disease conditions in a particular individual.

The invention uses a combination of two or more observations, which caninclude an image of at least a portion of an eye of a patient, and adata set corresponding to a response from at least a portion of an eyeof a patient. The two or more observations can comprise two images, animage and a data set, or two data sets. Images and data sets will bereferred to generally as information, which should be understood asnecessary to mean either images or data sets or both. The images includevisualization of a portion of an eye, and can include ophthalmic imagesusing confocal microscopy data, retinal polarimetry data, opticalcoherence tomography data, thermal image data, spectroscopic image data,refractometry data, and visible image data. The data sets include datathat is indicative of neurological disorders. For example, theneurological disorders include glaucoma, macular degeneration, diabeticretinopathy, Parkinson's disease, Alzheimer's disease, dyslexia,multiple sclerosis, optic neuritis, and inappropriate responses tocontrast sensitivity patterns. In some embodiments, the images arevisible images that include color fundus photography and black and whitefluorescein angiography.

The functional deficits of glaucoma and Alzheimer's Disease (hereinafter“AD”) include loss in low spatial frequency ranges in contrastsensitivity, and are similar in both diseases. Glaucoma, unlike AD,involves losses of optic nerve fiber layer originating in the retina. Atpresent, the only definitive diagnosis of AD involves identifyingamyloid plaques and neuro-fibrillary tangles in the neurons of thecortex by microscopic analysis of brain tissue. The invasive nature ofthe test necessitates that the test be performed after death. A testspecific for low spatial frequency deficits, as is available fordiagnosing glaucoma, would be useful in measuring similar deficits inAD. The Frequency Doubling Technique (hereinafter “FDT”), unlike manyother tests of visual function, does not require a high degree ofconcentration or of cognition. Because FDT takes only two minutes toadminister to both eyes, it is appropriate for subjects who havedifficulty concentrating for long periods.

Visual Deficits and Cognitive Function

Visual dysfunction appears to be a strong predictor of cognitivedysfunction in subjects with AD. Pattern masking has been found to be agood predictor of cognitive performance in numerous standard cognitivetests. The tests found to correlate with pattern masking includedGollin, Stroop-Work, WAIS-PA, Stroop-Color, Geo-Complex Copy,Stroop-Mixed and RCPM. Losses in contrast sensitivity at the lowestspatial frequency also was predictive of cognitive losses in the seventests. AD subjects have abnormal word reading thresholds correspondingto their severity of cognitive impairment and reduced contrastsensitivity in all spatial frequencies as compared to normal subjects.

Review of the Physiology of Vision

The visual system is believed to be made up of two parallel pathways:the M pathway and the P pathway. The pathways have individualizedfunction. There are a total of approximately 160 million rod and conecells in the normal eye. There are approximately 1.2 million ganglioncells (M and P cells) in the normal eye. The magnocellular or M pathway(comprising M cells) is sensitive to contrast sensitivity and motion. Mcells comprise both My cells (usually associated with contrastsensitivity) and Mx cells (usually associated with motion). There areestimated to be approximately 12,000 cells of the My type in the normaleye. The magnocellular M system has high contrast gain and saturates atrelatively low contrasts. The parvocellular or P pathway (comprising Pcells) is specialized for processing color and form. The parvocellular Psystem has a low contrast grain and more linear contrast visual stimuli.Losses specific to the M pathway have been identified in subjects withAD even in brain areas devoid of plaques and neurofibriallary tangles.The M pathway shows signs of significant cell loss in AD subjects. Instudies of primates, lesions have been found in the magnocellular layersof the lateral geniculate nucleus that does not impact contrastsensitivity for stationary gratings. However, such lesions do impactsensitivity for events involving motion or high temporal content. It hasbeen found in primates that lesions identified in the parvocellularlayers of the lateral geniculate nucleus (LGN) impacted contrastsensitivity for stationary or low temporal content events.

Review of the Pathology of Glaucoma

Glaucoma is a disease that is categorized by increasing internal eyepressure on the optic nerve. The compression of the nerve causes nervefiber morbidity and eventually cell loss. It is believed that the Mganglion cells of the visual system are impacted to a greater extentthan the P cells in glaucoma. M cells are fewer in number, have largeraxon diameter and larger receptive fields. Measurements of the visualfield, measurements of intraocular pressure and observation of changesin the nerve fiber layer and optic disc are utilized to diagnosis andmanage glaucoma. In glaucoma, the location of optic nerve change andpallor corresponds to location and density of visual field loss. Newtechnologies that detect image losses in the nerve fiber layer may havethe ability to detect glaucoma damage prior to the appearance ofmeasurable visual field losses.

Contrast sensitivity function is frequently reduced in glaucoma. Thereis a high correlation of low spatial frequency contrast sensitivity lossand the mean visual field loss in glaucoma. Higher rates of glaucomahave been found among patients with AD compared to a control group. Thediagnosis of glaucoma was based on the visual field defects or opticnerve cupping. Higher rates of glaucoma have also been found amongpatient's diagnosed with Parkinson's disease.

Visual field loss is a definitive sign of glaucoma and loss in visualfield correlates with loss in contrast sensitivity. The appearance ofoptic nerve fiber loss detected either by observation of the fundus ofthe eye or by the application of newer technologies also correlates withvisual field losses. The technology of the present invention may detectlosses in visual field at earlier stages than the traditionalinstrumentation of visual field loss can measure the losses. Theconclusion that optic nerve appearance and loss in the nerve fiber layerwould correlate with loss in contrast sensitivity is a reasonable one inthe case of glaucoma. Other diseases that have losses in contrastsensitivity also have losses in the nerve fiber layer and changes inoptic nerve appearance.

Frequency Doubling Technology and Glaucoma

FDT has been shown to detect glaucomatous changes at earlier stages thanare detected with stereophotographs, and has better sensitivity andspecificity than motion-automated perimetry. FDT is a better predictorof progressive field loss as measured by standard automated perimetrythan pattern electroretinography in a population of chronic open angleglaucoma. FDT is useful for detection of early glaucomatous visual fielddamage as compared to a Humphrey Field Analyzer and a high passresolution perimeter.

In the FDT instrument, the sinusoidal gratings are reversed (black towhite, and white to black) at 25 Hz. This stimulates the My ganglioncells. The contrast between the light and dark lines in the sinusoidalgrating targets is changed in order to determine a threshold ofperception of the target which is related to the healthy My typeganglion cells of the retina. A standard visual field test stimulatesall ganglion cell types. It is believed that the My cells are the firstganglion cells to die in glaucoma. Therefore, FDT provides earlierdetection of glaucoma. Subjects with AD have reductions in low spatialfrequency, the same function that the FDT tests. The same cells may beimpacted by AD compared to glaucoma, but the mechanism of cell deathdiffers.

Review of the Pathology of AD

There has long been controversy as to the primary cause of AD visualsymptoms. It is well documented that there are contrast sensitivityreductions, in particular at low spatial frequencies, in AD. Abnormalvisual perception and abnormal visuospatial processing are common withpatients diagnosed as having AD.

AD is a progressive degenerative disease of the brain leading tosenility and dementia. It is known to affect millions of people and thenumbers are rapidly growing. There are numerous forms of dementia, ADbeing only one, albeit the most devastating. Cognitive questionnaires donot accurately separate AD from other forms of dementia.

Numerous pharmaceutical companies are working on treatments for AD thatwill slow the progression and, in some cases, reverse the effects of AD.What is needed is a definitive, non-invasive test for AD prior to death.

AD is a large diameter neuron disease (Tsai 1991). Some researchers havefound microscopic amyloid plaques on retinal ganglion cells, but not inall cases, and not at all stages of the disease. Sadun (1990) found lossin M-type retinal ganglion cells, contrast sensitivity, and visualfields in the absence of plaques or tangles, but other researchers wereunable to reproduce these findings, suggesting that there is aprogression in the disease with varying symptoms. Most researchers agreethat amyloid plagues and tangles on cortical neurons is definitive ofAD. Because a longitudinal study on suspect AD patients is impossibledue to the invasiveness of the procedure, the progression of AD is notunderstood in detail.

Documentation of Retinal Ganglion

The degeneration in the retinal ganglion cells (RGC) of patients withAlzheimer's Disease was identified using histopatholic measure. Sadunfound degeneration of the retinal ganglion cells and axonal degenerationupon examining the retro bulbar optic nerves. There was a greaterfrequency of degeneration the more posterior the nerve was located. Apossible implication is that the retinal ganglion cell loss may besecondary to retrograde axonal degeneration.

Nerve Fiber Layer Analysis

A significant reduction in nerve fiber thickness in AD subjects comparedto normal subjects has been observed using OCT Humphreys.

The present invention provides novel systems and methods fornon-invasively diagnosing and tracking AD, based on a new theory of theprogression of AD. In one aspect of the theory, the optic nerves are anextension of the brain and therefore provide a window to the workings ofthe brain. In one embodiment, the Welch Allyn Frequency DoubledTechnology (FDT) visual field exam isolates retinal ganglion cells ofthe My type. These cells are associated with contrast sensitivity. Dueto their large diameter, they are generally, though not universally,believed to be some of the first cells to die in glaucoma. Presumably,the ganglion cells are damaged by an ischemic effect when passing thoughbent lamina cribrosa as a result of elevated intra-ocular pressure(IOP).

FDT has become the gold standard for early diagnosis and tracking ofglaucoma. Anecdotally, FDT has produced false positive diagnoses ofglaucoma, when subsequent analysis indicated diagnoses of tumor, maculardegeneration, diabetic retinopathy, multiple sclerosis, and otherneurological diseases.

In addition, various researchers have suggested that glaucomatous damagemay extend beyond the retinal ganglion cells into the lateral geniculatenucleus (LGN) and the visual cortex, and that the frequency doubledillusion may be mediated by a cortical loss of temporal phasediscrimination, thus again suggesting that neuron involvement is notlimited to ganglion cells.

FIG. 1A is a prior art diagram showing some of the physiology of the eyeand the brain in humans. FIG. 1B is a prior art cross sectional diagramshowing a feedback loop from the visual cortex to the LGN. In fact,approximately 80% of the axons feeding the LGN come from the visualcortex, while approximately 20% come from the retina.

Clinical evaluations are currently underway to determine the efficacy ofusing FDT to diagnose and track AD. One unanswered question is whetherFDT should be optimized to increase sensitivity and specificity.Although My cells are likely involved in AD, other forms of ganglioncells are also likely involved, such as Mx cells and P cells. Thus, theFDT zone shapes and sizes, spatial frequency, and temporal frequency maybe optimized to isolate different forms of ganglion cells and theirinteraction with feedback neurons from the visual cortex. At earlystages of the disease, plaques and tangles likely form in the visualcortex, thus sending an abnormal feedback to the LGN. This corticofugalfeedback affects the signals from the retina leading through the LGN tothe visual cortex. The result is an abnormal FDT finding. This effectmay or may not be associated with ganglion cell damage caused by atrophyat a given stage in the disease. The exact etiology will only be knownfor certain after cross-sectional and longitudinal clinical evaluationsare performed with subsequent histological analysis of the neurons. Themechanism for ganglion cells loss will likely differ from glaucoma inthat there need not be elevated IOP in AD.

Similarly, it is believed that other neurological disorders (such asmacular degeneration, diabetic retinopathy, optic neuritis,pappilledema, anterior ischemic optic neuropathy, and tumor) can bediagnosed and tracked by optimizing FDT (A Primer for Frequency DoublingTechnology, Johnson, 1998). AD and Parkinson's were not mentioned inthis product literature and are the subject of this treatise and latestinvention. An improved FDT technology, hereinafter FDT2, may be abetter, though slower, test for AD in that there are significantlysmaller interrogated areas than in the original FDT, thus leading todetection of loss at an earlier stage and more accurate tracking of AD.FDT2 can achieve resolution that is impossible with FDT, therebyproviding results that could not have been provided heretofore.

It is believed that at some point before the disease process hasadvanced to the stage where AD can be diagnosed using present daymethods, functional vision losses associated with AD becomes apparent inthe optic nerve, nerve fiber layer and retina. In one embodiment, theretina includes the peripheral retina. A variety of nerve fiber imagingtechniques and photographic techniques have demonstrated changes in theoptic nerve of subjects with AD. However, subjective testing relying onvisual fields and perimetry techniques prove unreliable in AD subjectsbecause of poor attentive skills. The FDT2 is a modified visual fieldtest of short duration. Additionally, low spatial frequency targets areused to sample test areas. This FDT2 instrument has the ability tomeasure field losses in AD subjects as well as localize retinal areasexhibiting low spatial frequency deficits.

Studies of the visual symptoms of AD findings observed in brain lesionshave shown that damage occurs in the visual association cortex and othercortical areas, as well as the primary visual cortex.

It is believed that at some point other than early in the diseaseprocess, losses associated with AD become apparent in the optic nerveand nerve fiber layer. Because it is a low spatial frequency test, theFTD will pick up such losses unlike other subjective testing such astraditional visual field techniques. The source of degeneration in thevisual system does not likely originate at the level of the retinalganglion cells. However, it seems these tissues are not spared in AD. Ithas long been demonstrated that pathologies originating in the higherareas of brain function eventually appear as pathology to the optic discand nerve fiber layer. It has been shown by means of stereo photos thatloss in the optic disc and nerve fiber layer are measurable in AD atsome stage.

There is evidence that there are right and left field advantages forsome visual functions. Because the FDT is a test of function in manyways similar to a standard visual field, it is possible to test splitvisual fields and therefore isolate in each eye right retinal functionand left retinal function. It is also possible to compare the functionof the right eye to the function of the left eye.

Histopathology studies of the optic nerve of subjects with AD werethought to show axonal degeneration originating from the retina. Thereis a loss of both large and small diameter ganglion cell layer neurons.These studies concluded there is a greater drop out of the largerneurons which project to the M layers of the lateral geniculate nucleus.Based on studies of primate retina and visual function, if there is aloss of cells along the M pathway, it would be expected that there wouldbe reductions in the ability to perceive motion or high temporal contentevents. Several studies of AD subjects have reported this. Indirectcomparisons of losses in both the P channels and the M channels showedthat the M channel function deteriorates at a greater rate than the Pchannel function in AD.

The Present Invention

It is believed that the optic nerves, as direct and intimate extensionsof the brain, are likely to be among the earliest nerves to exhibitchanges associated with various neurological disorders. It is believedthat these neurological disorders are observable by imaging the eye andmeasuring changes (or deviations) therein from what is considerednormal, as well as in neurological responses that are manifested in thebehavior and response of the eye, including the retina and the opticnerves. In addition, objective tests such as OKN, VEP and patternelectroretinograms (PERG) can be implemented in the systems and methodsof the invention. Objective tests are useful with infants andgeriatrics, as well as those who have difficulty communicating orfollowing specific directions.

Based on the image and/or data set information that is observed, theinvention provides an interpretive result. The term “interpretiveresult” is defined herein to mean a diagnosis (or a proposed diagnosis),or a change in physical condition or medical status over time, which amedical practitioner can consult in order to propose a course oftreatment for the individual patient in question. It is not to beinferred that the suggested diagnosis or indication of physicalcondition or medical status is to be taken as medical advice per se, butrather should be understood as an aid to a practitioner, who must stillapply his or her best medical judgment in counseling the patient.

Turning to FIG. 2, there is shown a schematic representation of anexemplary apparatus 100 suitable for use according to principles of theinvention. The apparatus 100 comprises a core portion 110 that in someembodiments can be portable or hand held. The core portion 110 comprisesa processor 112, which in some embodiments is a single board computer(SBC). The SBC is based on a microprocessor, such as an Intel x86 familymember or an equivalent processor. The processor 112 communicates with amicrocontroller (MCU) 114 by way of a bus 115, which is in oneembodiment an RS-232 bus. In some embodiments the MCU 114 is a MotorolaMC68332, which is a highly-integrated 32 bit microcontroller thatcombines high-performance data manipulation capabilities with peripheralsubsystems. The Motorola MC68332 comprises a 32 bit CPU, a systemintegration module, a time processing unit, a queued serial module and a2 Kbyte static RAM module with time processing unit emulationcapability. A memory device 116 is connected bi-directionally with theprocessor 112. The memory device can be any conventionalmachine-readable and -writeable storage device, including any or all ofRAM, DRAM, SDRAM, magnetic memory, and optical memory. The core portion110 also comprises a port 118, such as a universal serial bus (USB) orwireless port, for attaching external devices, such as a retina camera134, to the core portion 110. In some embodiments, an optional port 119is provided for attaching one or more electrodes 135, or other signalacquisition hardware, to the core portion 110.

The core portion 110 also comprises an eye monitoring device 120 formonitoring an eye of a person being tested or evaluated, includingmotion of the eye. In FIG. 2, the eye monitoring device 120 isrepresented by a video camera; however, another embodiment is describedhereinbelow, in which a simpler and less expensive device comprising oneor more linear charge-coupled device (CCD) arrays is presented. The coreportion 110 further comprises a display 122, for displaying informationto an operator of the instrument, which display 122 in some embodimentsis a liquid crystal display (LCD). Additional portions of the instrumentare attached to the core portion 110.

In some embodiments, the core portion 110 is connected to one or more ofoperator input devices, which in some embodiments are a keyboard 124, amouse 126, or other devices such as a microphone (not shown). Theoperator input devices communicate with the processor 112 by way of anyconventional wired or wireless connection. In some embodiments, the coreportion 110 is connected to one or more output devices such as a printer128 or a speaker (not shown) for communicating to a user of for creatinga hard copy of a record, such as the observations and assessments thatare generated during a test. By use of the operator input and outputdevices, an operator can introduce, and can record as hard copy,information such as a person's name, other identifying information, andother patent-related information such as tonometer intraocular pressure,patient-history, family history, blood pressure, vital signs,medication, and pupillometry, as well as any test conditions, such as anapplied stress. An applied stress can comprise any one of intra ocularpressure variation, blood pressure variation, oxygen concentrationvariation, exercise, flashing light, drug administration, administrationof insulin, and administration of glucose, or combinations thereof.

A display 130 is provided for displaying test patterns or other materialto a person being tested. The display 130 is connected to the coreportion 110 by way of an electrical connector and cable 131 and receivessignals from the MCU 114 as input to be displayed. The core portion 110also has attached thereto a response device 132, such as a mouse or abutton that can be manipulated or otherwise activated by a person beingtested to communicate responses to the MCU 114 by way of a cable andconnector 133. In some embodiments, the display 130 and the responsedevice are a unitary device, such as a touchscreen, and/or theconnections with the MCU 114 are made by wireless methods, such as RF orinfrared communication links using any conventional wireless technology(for example, 802.11a, 802.11b, or 802.11g).

The core portion 110 is connected to a retina camera 134 by way of theport 118, for viewing the fundus of an eye. In one embodiment, theretina camera 134 is a device such as the Welch Allyn Model 11820PanOptic™ Opthalmoscope, available from Welch Allyn, Skaneateles Falls,N.Y., with the addition of a video pickup to provide an electrical inputsignal to the core portion 110 of the apparatus 100.

In one embodiment, the retinal camera comprises a sensor such as a CCDarray that converts detected light into charge signals. The chargesignals are in general proportional to an illumination level and aduration of an exposure. The charge signals are converted, on a pixel bypixel basis, into analog signals or digital signals, as may be desiredusing conventional circuitry, such as switching circuitry, sample andhold circuitry, amplification circuitry, filters, and analog to digitalconverters. Digital representations of the images detected can beprovided with resolution defined by the capability of an analog todigital converter, ranging today from one bit resolution to 24 bitresolution, and with higher resolution as may become possible in thefuture. Both gray scale and color can be resolved. Additional detaileddescription of embodiments of video devices suitable for use accordingto principles of the invention is presented in U.S. Pat. No. 6,527,390B2 and U.S. Patent Application Publication No. US 2002/0097379 A1, bothof which are assigned to the common assignee of this application, andthe entire contents of each of which is hereby incorporated herein byreference.

In some embodiments, one or more electrodes 135 can be attached to thecore portion 110 by way of a port 119. The one or more electrodes 135,or other signal acquisition hardware, are used to acquire electricalsignals, for example, electrical potentials generated during testing,such as visually evoked potentials or other electrical signals useful indetecting responses of a person being tested.

A computer 136, which in various embodiments is a personal computer, alaptop computer, or another general purpose programmable computer ofsimilar or greater capability, is provided for analysis of images anddata sets that are collected in the course of testing a person. Theimages and data sets are communicated from the core portion 110 to thecomputer 136 by way of any of a wired connection link 140, such as anRS-232 communication bus, a wireless communication link 142, such as RFor infrared, or by transfer using removable media such as a CD-RW disc138 or a floppy or zip disk 144. In some embodiments, communication fromthe computer 136 to the core portion 110 is provided by any of the wiredlink 140, wireless link 142, and transfer using removable media such asCD-RW disc 138 and floppy or zip disk 144, so that commands in the formof programs, program modules, or individual commands to perform aspecific action can be downloaded from the computer 136 to the coreportion 110, or can be accessed by the core portion 110 while residentat the computer 136. To this end, each of the computer 136 and the coreportion 110 are provided with the appropriate ports and/or read-writedevices for reading and writing media as necessary. The core portion 110and the computer 136, as well as the other attached devices, are poweredby conventional line voltage connections using wall plugs and powersupplies, or by the use of batteries, as appropriate, depending on theintended use of the apparatus, e.g., in an office setting, or in a fieldsetting.

FIGS. 3A-3D show generally an approach to providing an eye monitoringdevice 120 useful for monitoring the motion of an eye. FIG. 3A shows aschematic diagram 200 of the disposition of an eye monitoring device 120relative to an eye 260 of a person being tested. In addition, FIG. 3Aindicates at a high level the relative disposition of components withinthe eye monitoring device 120, which is a hand held, portable device inthe embodiment depicted. The eye monitoring device 120 comprises, in oneembodiment, a handle 210 that provides a griping structure for apractitioner to hold and position the eye monitoring device 120 relativeto the eye 260. The handle 210 is adapted to contain the battery usefulfor operating the device and the electronics useful for manipulatingdata, providing control signals, and communicating commands and data toand from the eye monitoring device 120. A head portion 220 of the eyemonitoring device 120 contains a display 230, such as a CRT, fordisplaying a test pattern to the eye 260. The head portion 220additionally contains one or more sensors 240 that are aimed to detectlight reflected from a surface of the eye 260. The one or more sensors240 in one embodiment are 1024×1 CCD arrays capable of detecting lightat each of 1024 pixel locations, and providing an electrical signalproportional to an intensity of light detected at each pixel. The one ormore sensors 240 are focused on a surface of the eye 260 by optics 250,which can be constructed of one or more components made from anyconvenient optically transmissive material such as glass or plastic.

FIG. 3B shows a diagram 202 that depicts the interrelationship among thefeatures of an eye 260 of a person being tested, and the areas 242, 244of the eye sensed by two sensors. The eye 260 is being viewed straighton in FIG. 3B, and features of the eye 260 including the white area 262,the iris 264, and the limbus 266 of the iris 264 are represented. Twoareas of focus 242, 244 of two sensors, such as the one or more sensor240 of FIG. 3A, are depicted on the surface of the eye 260. One area offocus 242 is positioned along an imaginary horizontal line (i.e., line268 in FIG. 3C) passing through the center of substantially circularlimbus 266. A second area of focus 244 is positioned along a secondimaginary horizontal line parallel to the first imaginary horizontalline, but above (or alternatively, below) the first area of focus 242 byan offset of dimensions of millimeters. Each of the two sensors (notshown) can detect an intensity of light reflected from differentlocations on the surface of the eye 260. A white portion 262 of thesurface of the eye 260 will in general reflect light more strongly thana darker portion of the surface of the eye 260, such as the iris 264, orthe pupil of the eye situated within the iris 264. As the eye moves, thechange in intensity of light reflected from the white portion 262 ascompared to the intensity of light reflected from the iris 264 istracked. Position is measured as a pixel location counted from one endof a sensor 240. The position of the change in intensity of reflectedlight corresponds to the location of the limbus 266. When the twosensors detect a change in the position of the limbus, the direction ofmotion of the eye can be deduced. By applying standard discrete timeanalysis, the velocity of the motion can also be deduced as x-axisvelocity=k(DX/DT), where k is a constant, DX is a change in positionalong an X axis, and DT is a change in time, and a y-axis velocity canbe determined as y axis velocity=k(DY/DT), where DY is a change inposition along a Y axis. As is well known in the mathematical analysisarts, two data inputs that are independent with respect to x- and y-axismotion are sufficient to determine both motions and their velocities.

FIG. 3C shows a diagram 204 that depicts the interrelationship betweenthe features of an eye 260 of a person being tested, and the area 242 ofthe eye sensed by one sensor. In FIG. 3C, the features corresponding tothose described with respect to FIG. 3B are indicated by like numerals.In the event that the eye 260 only moves horizontally, the x-axis motionis the only motion that is detected. Accordingly, only one data inputthat tracks x-axis motion is required, and the area 242 aligned alongthe centerline 268 of the limbus 266 is sufficient. A procedure usefulin constraining the motion of the eye 260 to the horizontal direction isdescribed next.

FIG. 3D shows a diagram 206 that depicts a test pattern 282 and afixation signal 290 that is useful for fixating an eye 260 of a personbeing tested when one sensor is employed in the eye monitoring device120. The CRT 230 of FIG. 3A provides a frame 280 of visually displayedinformation. A test pattern 282 is disposed within frame 280, comprisingone or more vertical lines 284 that can be traversed horizontally over abackground 286. The eye 260 of the person being tested will in generalattempt to follow the motion of the one or more lines 284. However,there in general can be a wandering of the gaze of the eye 260 in anupward or downward direction while the eye 260 attempts to follow thehorizontal motion of the lines 284. The fixation signal 290, which is aprominent solid line segment disposed horizontally across the testpattern 282, within a field of view of substantially 5 degrees totalangular height or less, is provided to prompt the eye 260 to fixatevertically along the horizontal line 290 while not interfering with theproclivity of the eye 260 to follow the horizontal motion of the one ormore vertical lines 284.

FIG. 4 is a flow chart 400 showing the steps in the operation of theinstrument and method of the invention, or alternatively, showing theinterrelationships among the modules comprising apparatus according tothe invention. The description will be presented in terms of modules,but those of ordinary skill will also understand the figure asdescribing the steps of performing the method of the invention.Information is collected by imager 410 and data set collector 420 asnecessary. In one embodiment, the information is a plurality of images.In another embodiment, the information is a plurality of data sets. Inyet another embodiment, the information comprises at least one image andat least one data set. The information is transferred to the dataanalysis module 430 for analysis. A memory module 470 in bi-directionalcommunication with the data analysis module 430 can record informationsent from the data analysis module 430 in raw form, in analyzed form, orin both forms. Furthermore, the memory module 470 can store information,including as an archival storage, and can provide stored information tothe data analysis module 430 as required. For example, the memory module470 can provide information that was recorded during a previous visit ofa patient to a medical practitioner for the purpose of comparing currentinformation observed from the patient with historical information.Archived information can be stored locally or at a remote location. Aremote storage capability, which is not shown, can be connected tomemory module 470 and or to data analysis module 430 by any convenientmeans, including wire connection, wireless connection, and by thephysical movement of storage media, such as floppy disks, CD-ROM disks,DVD disks, magnetic tape, memory cards, and similar moveable storagemedia.

A superposition module 440 is in bi-direction communication with thedata analysis module 430. Information can be sent from the data analysismodule 430 to the superposition module 440, and data that has beensubjected to superposition can be sent from the superposition module 440to the data analysis module 430. As described below with respect to FIG.5, the superposition module 440 in some embodiments comprises aplurality of other modules.

The data analysis module 430 is in communication with a data outputmodule 450, which can provide information to a user. The data analysismodule 430 is optionally in communication with a report module 460,which can provide reports to a user. The data analysis module 430 isoptionally in communication with a display module 480 that can displayimages, sets of data, and superpositions of information to a user forvisual examination of the information.

FIG. 5 is a diagram 500 depicting components of a superposition module440 according to the invention. The superposition module 440 canoptionally comprise first and second identification modules 510, 520that identify first and second fiduciary points in an image or a dataset. In some embodiments, the first and second identification modules510, 520 are the same module. The superposition module 440 alsooptionally comprises an orientation module 530, a scaling module 540,and a correspondence module 550. The orientation module 530 orientsimages or data sets to be superimposed about a fiduciary point so that afirst metric and a second metric are oriented in selected orientations.The scaling module 540 scales an image or data set so that a first unitof measure associated with the first metric and a second unit of measureassociated with the second metric in each image or data set to besuperimposed are substantially equal to selected first and secondvalues. The correspondence module 550 creates a one-to-onecorrespondence between the fiduciary point, the first metric and thesecond metric in a first image or data set to be superimposed with thefiduciary point, the first metric and the second metric in a secondimage or data set to be superimposed.

In some embodiments, the first metric and the second metric are firstand second axial directions. In one embodiment, the first and secondaxial directions are coplanar but not parallel axial directions, such astwo axes, for example the x and y axes in a Cartesian coordinate system.Other coordinate systems can be used equally well. In such anembodiment, the first unit of measure associated with the first metricis a length along the first axial direction, such as a number of unitsalong an x-direction, and the second unit of measure associated with thesecond metric is a length along the second axial direction., such as anumber of units along a y-direction. In other embodiments, the firstmetric is a first axial direction, the second metric is an angulardisplacement from the first axial direction, the first unit of measureassociated with the first metric is a length along the first axialdirection, and the second unit of measure associated with the secondmetric is a unit of angular measure. For example, the first metric is aheading or compass direction that is considered to be zero degreesrelative to an origin (i.e., due North on a map), and the first unit ofmeasure is a geometric distance along the heading (i.e., a radius of acircular arc), the second metric is an angle (i.e., θ degrees clockwiserotation), and the second unit of measure is an angular value, such asθ=90 degrees. When a plurality of images, a plurality of data sets, orat least one image and at least one data set are scaled, rotated and/ortranslated such that corresponding first and second metrics are made tocoincide, the plurality of images, the plurality of data sets, or the atleast one image and at least one data set will be capable of beingsuperimposed.

In the display of such images, one can present the images side by side,or in superimposed configuration, one upon the other. The images can becompared by simple superposition, to show interrelationship of one ormore features that appear in each. Alternatively, by superimposing oneimage on the “negative” of another, it is possible to make thedifference (or the change between a first image and a second image)readily apparent. For example, a new feature appearing in a later imagewill become the only feature (or a highlighted image) displayed in adisplay comprising a “negative” of a first image superimposed upon (orsummed with) a second, later, image. Images can be displayed in falsecolor as well, so that regions of data sets that comprise substantiallysimilar values can be readily discerned. For example, an image in whicha first color is used to represent data points below a threshold valueand a second color is used to represent data points exceeding thethreshold value provides a display for a viewer in which the regionshaving specified ranges of values are readily identified. As required,more than two ranges can be assigned, and corresponding different colorscan be used in the display of the data set.

FIG. 6 is a diagram 600 showing a region of frequency space having bothtemporal and spatial frequency variations, and indicating a typicalperson's reaction thereto, as is known in the prior art. FIG. 6 is basedon observations made by D. H. Kelly, which results were reported someyears ago. In FIG. 6, the horizontal axis 610 is a logarithmic axis thatrepresents the temporal frequency in cycles per second (cps) rangingfrom close to zero to approximately 100 cps. In FIG. 6, the verticalaxis 620 is a logarithmic axis that represents the spatial frequency incycles per degree (cpd) ranging from close to zero to approximately 20cpd. In this circumstance, degrees are measured as angular measure onthe retina of an eye. As can be seen, there is a region 630 extendingfrom about 7 cps to about 60 cps and from about 0.1 cpd to about 2 cpd,which region 630 is labeled “Spatial Frequency Doubling.” The region 630further includes a point indicated by the cross 635 that is in someembodiments a target spatial and temporal frequency operating point inthe vicinity of 25 cps and 0.3 cpd. Within the Spatial FrequencyDoubling region 630, a person with normal vision see a pattern thatappears to be doubled in spatial frequency from its actual spatialfrequency. Persons with compromised vision, or with other neurologicaldifficulties, have difficulty perceiving the doubled spatial frequencypattern, or see it only at higher contrast.

FIGS. 7A and 7B are drawings that depict a display space 710 that issegmented and includes an illustrative contrast pattern 720. In FIGS. 7Aand 7B, one segment 715 includes a high contrast pattern 720 and onesegment 715 includes a lower contrast pattern 720′, respectively. Eachof FIGS. 7A and 7B include a central region 730 that can in someembodiments be used to locate a fixation element, or a differentcontrast pattern than the patterns shown in segment 715. As may beunderstood from comparison of FIGS. 7A and 7B, the more stronglycontrasting pattern 720 of FIG. 7A can be transformed into the lowcontrast pattern of FIG. 7B by decreasing the dynamic excursion (ordynamic range) of the signal comprising high contrast pattern 720. Highcontrast pattern 720 is generated by providing a sinusoidally varyingsignal having bright and dim extremes, or strongly illuminated regionsand weakly illuminated regions. It is expected that those withcompromised neurological condition will perceive the contrast signal todisappear at a higher contrast level threshold than those with normalvision and normal neurological conditions. Dyslexia may be indicated byan inappropriate response to contrast sensitivity tests, because indyslexia the eye and the brain collaboratively misinterpret the spatialrelationships in data.

FIGS. 8A, 8B and 8C are diagrams that show the relationship between animage and a data set, two images taken at different times, and a seriesof images, false color data representations, and data sets,respectively. As depicted in FIGS. 8A, 8B and 8C, the interrelatedimages and data sets are displayed side-by-side. It will be understood,perhaps most readily by considering the two images of FIG. 8B, that twoor more pieces of information can also be superimposed. Carefulcomparison of the leftmost image of FIG. 8A with either of the images ofFIG. 8B will show that the leftmost image of FIG. 8A is larger in sizethan either image of FIG. 8B. As is seen in the images of FIG. 8B, manyfeatures of one image are also present in the other image, and the twoimages could easily be presented as either the superposition of one onthe other, or the superposition of one over the negative image of theother, thereby highlighting the differences between the two images. Inone embodiment, viewing the information in side-by-side presentationmakes it easier to compare information, and may allow certain forms ofanalysis, but requires the viewer to synthesize the data to find certaincorrespondences. In other embodiments that use superposition, benefitsthat accrue include the ability to highlight, the ability to subtract orotherwise process information, and the ability to assure that two piecesof information are representative of the same area or feature.

In FIG. 8A, the left image is an image 805 of a retina of an eye,including a macula 810 near the center of the image. In FIG. 8A, theright image 808 is a map of a contrast level observation, in which thecentral region 730 corresponds to the macula 810, and the region 715having the contrast pattern 720 therein is intended to convey theinformation that the observed response of the eye was acceptable in thatregion 715.

In FIG. 8B, the left image 805′ is a first image of a retina of an eye,in which the macula 810 is again visible. The right image is an imagethat represents a second image of the same retina taken 6 months later,in which the macula 810 is again visible. However, in the later rightimage 805″, a new feature 820 appears to the left of the macula 810. Theside-by-side presentation in FIG. 8B is intended to show that for highlysimilar images, it is relatively easy to compare two or more images, ascan be seen in a comparison of the two images in FIG. 8B, wherein alarge number of features can be observed to be substantially common toboth images, such as the position and shape of imaged blood vessels 830.While the new feature 820 is readily apparent, it is not clear from theimage whether the new feature 820 represents an active proliferation ofcapillaries (i.e., blood is still circulating in blood vessels) orwhether the new feature is a blood clot that has long since ceased tocirculate. More information is available from a consideration of theimages shown in FIG. 8C.

FIG. 8C comprises four pieces of information. The leftmost image is theimage 805″ as seen in FIG. 8B, right side. This is a high resolutionimage that is displayed on a pixel by pixel basis, wherein much detailis available for analysis. Again, the feature 820 is visible. The nextpanel in FIG. 8C (i.e., the second image from the left) is a false coloroxygen saturation view 820A of the region of the retina in the vicinityof the new feature 820. In the second image 820A, one can discern thatthe new feature 820 is a region centered on a junction 825 of bloodvessels 830, which gives further credence to the analysis that thefeature 820 represents blood high in oxygen. The next image 806 (i.e.,the third image from the left) is a false color thermal image taken atlower resolution that the second image from the left (i.e., 4 by 4pixels rather than one-by one pixel), which image shows the new feature820, for example, as a red (false color) square region 820′ at thejunction 825 of a yellow (false color) blood vessels 830. The red falsecolor is representative of a higher temperature than the immediatesurroundings, suggesting that the new feature 820 is a proliferation ofcapillaries that comprises fresh, warm blood, rather than an old bleedwhich would have reached the same background temperature as thesurrounding tissue, and therefore would have been represented by thesame color (green). A second red false color region 832 is also shown inthe false color image, the second red false color region correspondingto the macula 830, which is rich in blood vessels, and therefore wouldbe expected to be somewhat warmer than the surrounding area. Therightmost panel of FIG. 8C is a representation 809 of a data setobtained from a contrast sensitivity measurement, in which the centralregion 812 corresponds to the macula 810 of the leftmost image 805″. Thedata set is represented at a rather low resolution as compared to theleftmost image 805″, for example using a 10 pixel by 10 pixelresolution. The gray region 850 of the contrast sensitivity data setrepresents a region of severely degraded response, which corresponds tothe location of the new feature 820 in the leftmost panel of FIG. 8C.One can then recognize from the aggregation or interrelation of images805″, 820A, 806, and 809, that the new feature 820 gives all theindications of a region representing an active capillary structure, thestructure negatively impacting the vision of the eye underconsideration.

FIG. 9 is an illustrative schematic in exploded form showing therelationship among superimposed images and/or data sets. In FIG. 9 thereare three parallel planes 910, 920 and 930. Situated on each plane is animage or a map of a data set. For example, there appears on plane 910image 912 that is a photographic image of the fundus of an eye such asis captured by a retinal camera 134. Along axis A, which is denoted by adotted line extending between the planes 910, 920, 930, there is inimage 912 a spot 914, which corresponds to the area of capillariesdescribed as the new feature 820 of FIGS. 8B-8C. Along axis B, which isalso denoted by a dotted line extending between the planes 910, 920,930, there is in image 912 a macula 916, which corresponds to the maculaof FIGS. 8A-8C. There are blood vessels 913 that have a junction 915, aswell as other features visible in image 912.

In plane 920 of FIG. 9 there appears an image that is a false colorthermal image taken at a lower resolution than the second image from theleft (e.g., 4 by 4 pixels rather than one-by one pixel), which imageshows the new feature 820 as a red (false color) rectangular region 924at the junction 925 of yellow (false color) blood vessels 923. The Aaxis passes through the rectangular region 924 representing the falsecolor image of the new feature 820. The B axis passes through the squarefalse color region 926 corresponding to the macula 916 of the eye.

In plane 930 of FIG. 9 there appears a map 932 corresponding to a dataset recorded as a result of a contrast sensitivity test. In the map 932there is a fixation pattern 936 which is the area upon which the gaze ofthe eye under test is expected to fall, and as described above, is alocation where the gaze of the eye can be observed to fall byinstrumentation of the invention. Accordingly, the fixation pattern 936,or a selected pixel of the fixation pattern 936, such as the center ofthe fixation pattern 936, can be placed along Axis B so as to coincidewith (or to be superimposed upon) the image of the macula 916 and thefalse color image 926 of the macula. Also, the region 934 of the map 932corresponding to the data set obtained in the contrast sensitivity testindicates a diminution in the ability of the eye to perceive thecontrast pattern, which diminution is denoted by a gray hue in area 934.In some embodiments, the depth or intensity of the gray hue, or the useof a range of false colors, can be used to represent the severity of thediminution of perception. The region 934 is aligned with Axis A,corresponding to the area of the retina having the new feature 820 thatis depicted as region 914 of the fundus photograph 912. As needed, thesizes of one or more of the various images and maps or otherrepresentations of data sets can be expanded or contracted so thatsuperposition is possible. Furthermore, any of the images orrepresentations of data sets can be translated and/or rotated to orientone with respect to another so that superposition can be accomplished.As is understood in the geometric arts, superposition can be attained bysuperimposing two selected points in a first image with thecorresponding two selected points in a second image. Superposition canalso be attained by defining a pair of coplanar but not parallel vectorsin each image, causing the dimensions of the images to be commensurateby expanding or contracting at least one image as needed, and aligningthe vectors. Superposition can also be accomplished by defining anorigin and a vector in each image, causing the dimensions of the imagesto be commensurate by expanding or contracting at least one image asneeded, and aligning the origins and the vectors.

According to principles of the invention, it is possible to determineblood glucose by measuring the eye of a patient using an instrument asshown in FIG. 10, and described in more detail below.

The operation of the instrument is based on the observation that inhumans, and perhaps in other animals, the retina of the eye has one ofthe fastest metabolic rates in the body. Diabetes is a disease that ischaracterized by poor control of blood glucose. Diabetics attempt tocontrol their blood glucose levels by balancing food intake, exerciseand medication, such as insulin or other medications. In order todetermine whether and how much insulin to administer, the blood glucoselevel of the individual must be measured. Today, diabetics can berequired to draw blood, commonly by pricking a finger, several times aday. The procedure of drawing blood can be painful and invasive, andcompliance with a strict medical regimen may be affected in a negativeway.

The blood glucose determination apparatus of the invention, and itsmethod of use, may have applicability in blood glucose monitoring indiabetics, with several advantages. First, the measurement does notrequire the drawing of blood, and is therefore painless. In addition,the measurement device will not require the use of consumables, such aschemicals or treated strips that interact with drawn bodily fluids. Thelack of consumables, other than a replaceable battery, will reduce theoperating cost per test, making testing possible at lower operatingcosts than in conventional tests that require interaction of a bodilyfluid with a test medium. In addition, the absence of consumables willmake testing more convenient in that the user does not need to rememberto transport consumable items when he or she travels from home, evenduring the day. Another benefit is the fact that the test will berelatively unobtrusive and not embarrassing, so that it can be performedquickly and in public settings as may be required.

Experimenters have studied the effects of glucose on the retina, theheart, and the kidneys for many years. These organs are well-known to benegatively affected in persons suffering from diabetes. One relationthat has been noted is the ability of the retina to observe or determinecontrast, which varies with the blood glucose level. In particular, arelation between a person's visual contrast sensitivity and the person'sblood glucose level may provide a basis for measuring the blood glucoselevel. It may be necessary or advantageous to calibrate the measurementby the use of a blood glucose measurement using drawn blood. However,once the calibration is performed, the necessity to draw blood to makeactual measurements is obviated. The calibration might also be performedby using different blood glucose levels, e.g., high blood glucose,normal blood glucose, and low blood glucose, which levels may be inducedby deliberate administration of foodstuffs or by the deliberatewithholding of food and having the person to be tested perform exercise.

The apparatus 1000 of FIG. 10 is in one embodiment a hand-held devicethat measures a person's visual contrast sensitivity in the same waythat the FDT device measures contrast sensitivity in persons exhibitingglaucoma and/or other neurological disorders. As shown in FIG. 10, theapparatus 1000 comprises a power supply 1010 such as a battery andelectronics 1020 for generating and displaying a contrast pattern 1030that appears on a display 1040 and for computing a result of a bloodglucose measurement. In one embodiment, the electronics 1020 comprises amicroprocessor or microcontroller and memory, as well as the necessarysignal acquisition and conditioning hardware for responding to commandsfrom the user, as well as software that may be recorded in nonvolatileform in a machine-readable medium. In one embodiment, the display 1040will be an LCD similar to those used in present-day camcorders. In otherembodiments, other display technology may be used. The apparatus 1000also comprises a lens 1050 for focusing an image of the contrast pattern1030 so that the image may be viewed by an eye 1070 of a user. Thecontrast pattern 1030 can also include a fixation element 1032, forassisting the user in fixing his or her gaze on a particular location ofthe display. The apparatus 1000 also can comprise an optical element1060 useful for changing a size of the image and/or for causing thelight from the image to be correctly oriented for the user to view theimage. In some embodiments, the optical element 1060 is a mirror, whichcan be a planar mirror, a convex mirror, or a concave mirror asrequired. The eye 1070 as shown comprises an iris 1072 and a lens 1074,as is commonly found in eyes for causing an image to fall on a retina1076 of the eye.

In use, the user holds the apparatus 1000 in a position such that theuser can observe the contrast pattern 1030 and the fixation element1032. The fixation element 1032 help to insure that the contrast pattern1030 will fall on the same portion of the user's eye 1070, such that thesame area of the retina 1076 of the eye 1070 is interrogated. The areacan be any area of the retina that represents the test subject'sreaction to blood glucose level or concentration. In some embodiments,the area is the macula of the eye 1070, in which case the contrastpattern 1030 and the fixation element 1032 are coincident. For example,the contrast pattern 1030 can be centered on the fixation element 1032.In one embodiment, the user can activate a button 1080 on the apparatus1000 during a time when he or she can see the contrast pattern 1030. Thebutton 1080 is connected electrically to the electronics 1020. In oneembodiment, the user releases the button 1080 to indicate that the usercan no longer distinguish the contrast sensitivity pattern 1030, therebycompleting a test cycle. The contrast sensitivity pattern 1030 firstappears with dark lines and light lines, which respectively becomelighter and darker with time. At some point, either when the two sets oflines in the contrast sensitivity pattern 1030 have the same opticalcharacteristic and cease to be distinguishable, or when the user is nolonger able to distinguish between the light and dark sets of lines, theuser would be expected to release the button 1080. After the electronics1020 processes the data it receives, and computes a blood glucose levelfor the user, the result may in some embodiments be displayed to theuser by being presented on the display 1040 of the apparatus 1000 in anyof an alphanumeric format, a pictorial format (i.e., a graphic or anicon), an audible signal provided by a speaker 1082, a tactile signalprovided by a vibrator, or any combination of signals. In alternativeembodiments, the result can be transferred, for example by wirelesscommunication, to another device, such as a personal digital assistant,a cellular telephone, a computer, a data recorder, a printer, or anexternal display. For example, a person may wish to have a result thatindicates a serious abnormality, such as severe hypoglycemia, reportedto another trusted party to make sure that appropriate medicalintervention takes place.

Those of ordinary skill will recognize that many functions of electricaland electronic apparatus can be implemented in hardware (for example,hard-wired logic), in software (for example, logic encoded in a programoperating on a general purpose processor), and in firmware (for example,logic encoded in a non-volatile memory that is invoked for operation ona processor as required). The present invention contemplates thesubstitution of one implementation of hardware, firmware and softwarefor another implementation of the equivalent functionality using adifferent one of hardware, firmware and software. To the extent that animplementation can be represented mathematically by a transfer function,that is, a specified response is generated at an output terminal for aspecific excitation applied to an input terminal of a “black box”exhibiting the transfer function, any implementation of the transferfunction, including any combination of hardware, firmware and softwareimplementations of portions or segments of the transfer function, iscontemplated herein.

While the present invention has been explained with reference to thestructure disclosed herein, it is not confined to the details set forthand this invention is intended to cover any modifications and changes asmay come within the scope of the following claims.

1. Apparatus for performing multiple procedures involving the retina ofthe eye, said apparatus comprising: at least one imager for imaging atleast a portion of an eye of a patient, said at least one imagerconfigured to provide image data comprising at least two data typesselected from the group consisting of data from ophthalmic images usingconfocal microscopy data, retinal polarimetry data, optical coherencetomography data, thermal image data, spectroscopic image data,refractometry data, and visible image data; and a data analysis modulethat interrelates data from said at least two data types to provide aninterpretive result that is indicative of a presence of an abnormalitythat appears to involve a retinal portion of the eye, and where saidabnormality could actually involve, at least in part, an abnormality ofthe brain.
 2. Apparatus as recited in claim 1, further comprising adisplay module that provides a display of interrelated data to a user.3. Apparatus as recited in claim 1, further comprising a data outputmodule that reports interrelated data from said at least two data types.4. Apparatus as recited in claim 1, further comprising a report modulethat reports said interpretive result.
 5. Apparatus as recited in claim1, further comprising a single output module that reports interrelateddata from said at least two data types and said interpretive result. 6.Apparatus as recited in claim 1, further comprising a superpositionmodule for superimposing data obtained from at least two images. 7.Apparatus as recited in claim 6, further comprising a display fordisplaying superimposed data obtained from at least two images. 8.Apparatus as recited in claim 7, wherein said superimposed data obtainedfrom at least two images comprises data obtained from at least twodifferent data types selected from the group consisting of data fromophthalmic images using confocal microscopy data, retinal polarimetrydata, optical coherence tomography data, thermal image data,spectroscopic image data, refractometry data, and visible image data. 9.Apparatus as recited in claim 1, further comprising a memory for storingimage data.
 10. Apparatus as recited in claim 9, wherein said memory forstoring image data is configured to store and to selectively retrievedata from at least one image for determining changes induced in responseto an applied stress.
 11. Apparatus as recited in claim 10, where saidapplied stress is selected from the group consisting of intra ocularpressure variation, blood pressure variation, oxygen concentrationvariation, exercise, flashing light, drug administration, administrationof insulin, and administration of glucose.
 12. Apparatus as recited inclaim 9, wherein said memory for storing image data is configured toarchivally store image data.
 13. Apparatus as recited in claim 1,wherein said data analysis module is configured to automaticallydetermine a presence of an abnormality.
 14. A method of treating apatient, comprising the steps of: performing an examination of a patientusing the apparatus of claim 1; and treating said patient based at leastin part on a result obtained from said examination.
 15. The apparatus ofclaim 1 where said at least two data types include a first data type anda second data type, and where said first data type is optical coherencetomography data and where a second data type is visible image data andwhere an interpretive result indicates a presence of glaucoma orAlzheimer's disease based upon said two data types.